| Autor: |
Korn SM; Institute for Molecular Biosciences, Biomolecular Resonance Center (BMRZ), Goethe University Frankfurt, Max-von-Laue-Str. 7-9, 60438 Frankfurt, Germany., Von Ehr J; Institute for Molecular Biosciences, Biomolecular Resonance Center (BMRZ), Goethe University Frankfurt, Max-von-Laue-Str. 7-9, 60438 Frankfurt, Germany.; IMPRS on Cellular Biophysics, Max-von-Laue-Str. 7-9, 60438 Frankfurt, Germany., Dhamotharan K; Institute for Molecular Biosciences, Biomolecular Resonance Center (BMRZ), Goethe University Frankfurt, Max-von-Laue-Str. 7-9, 60438 Frankfurt, Germany., Tants JN; Institute for Molecular Biosciences, Biomolecular Resonance Center (BMRZ), Goethe University Frankfurt, Max-von-Laue-Str. 7-9, 60438 Frankfurt, Germany., Abele R; Institute for Biochemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany., Schlundt A; Institute for Molecular Biosciences, Biomolecular Resonance Center (BMRZ), Goethe University Frankfurt, Max-von-Laue-Str. 7-9, 60438 Frankfurt, Germany. |
| Abstrakt: |
The family of scaffold attachment factor B (SAFB) proteins comprises three members and was first identified as binders of the nuclear matrix/scaffold. Over the past two decades, SAFBs were shown to act in DNA repair, mRNA/(l)ncRNA processing and as part of protein complexes with chromatin-modifying enzymes. SAFB proteins are approximately 100 kDa-sized dual nucleic acid-binding proteins with dedicated domains in an otherwise largely unstructured context, but whether and how they discriminate DNA and RNA binding has remained enigmatic. We here provide the SAFB2 DNA- and RNA-binding SAP and RRM domains in their functional boundaries and use solution NMR spectroscopy to ascribe DNA- and RNA-binding functions. We give insight into their target nucleic acid preferences and map the interfaces with respective nucleic acids on sparse data-derived SAP and RRM domain structures. Further, we provide evidence that the SAP domain exhibits intra-domain dynamics and a potential tendency to dimerize, which may expand its specifically targeted DNA sequence range. Our data provide a first molecular basis of and a starting point towards deciphering DNA- and RNA-binding functions of SAFB2 on the molecular level and serve a basis for understanding its localization to specific regions of chromatin and its involvement in the processing of specific RNA species. |
